Contamination, dynamics, and health risk assessment of pesticides in seawater and marine samples from the Seto Inland Sea, Japan.

We assessed the contamination, dynamics, and health risks of the pesticides cyanazine, simetryn, fenarimol, isoprothiolane, diazinon, irgarol, fenitrothion, and diuron in marine samples (seawater, sediments, plankton, fish, and other edible organisms) at various locations in the Seto Inland Sea in Japan in 2016 and 2017. Pesticide concentrations were highest at sampling sites close to the coastline, and mean concentrations in seawater were slightly higher in surface water than in bottom water. All eight pesticides were detected in plankton. Diazinon concentrations (77-387 ng/g dw) were highest in sediments and cyanazine was the most frequently detected pesticide (88%, n = 17) in sediments. Only cyanazine (2.7-41.9 ng/g dw), simetryn (1.0-34.3 ng/g dw), and diazinon (6.3-308.8 ng/g dw) were detected in fish and other edible marine organisms. Based on the calculated bioconcentration factor, the results showed that plankton, fish, and marine animals bioaccumulated pesticides. The highest hazard quotients were calculated for diazinon in red seabream and greenling, indicating a possible risk to consumers. It is, therefore, imperative to promote strict implementation of pollution control, integrated pest management practices, and policy formulation on pesticides. Usage of diazinon must be controlled and monitored to ensure large residues do not reach aquatic ecosystems and marine coastlines.

Dynamics and Mass Balance of Polycyclic Aromatic Hydrocarbons in and Around the Seto Inland Sea, Japan.

Polycyclic aromatic hydrocarbons (PAHs) were analyzed to elucidate the distribution, ecological risk, pathways, and fluxes of these pollutants in and around the Seto Inland Sea, an industrialized coastal region of Japan. High molecular weight PAHs (5-6 rings) were primarily found in regions close to the bay estuaries, and their proportions decreased at distances further from the estuaries (offshore areas), where low molecular weight PAHs (2-4 rings) were more ubiquitous. Screening-level risk assessments revealed that the PAHs found in the sediments should have no adverse effects on benthic communities. A mass balance for PAHs in the Seto Inland Sea, calculated based on data collected in the field and published literature findings, showed the PAH flux into the Seto Inland Sea from atmospheric deposition were ca. 6 times higher than that from riverine inflows. Comparison of the amount of the PAH mass flux between the Seto Inland Sea and the sea of the Europe and Asian countries indicated that the Seto Inland Sea is less polluted than the Gulf of Lion, the Mediterranean Sea, and the Bohai Sea, China and more polluted than the Yellow Sea. This paper is the first to determine the fluxes of PAHs in the coastal region of Japan.

Accurate Evaluation of Residual Common Bile Duct Stones by Endoscopic Ultrasound: A Two-Step Check Method for Residual Stone Clearance.

BACKGROUND/AIMS: Residual common bile duct (CBD) stones occasionally become symptomatic after stone removal with endoscopic retrograde cholangiopancreatography (ERCP) upon removal of the endoscopic biliary stent (EBS). An accurate evaluation of residual stones before stent removal is necessary. This study evaluated a new two-step check method using endoscopic ultrasound (EUS) for the detection of residual stones after ERCP stone removal. METHODS: Fifty-six patients who underwent CBD stone removal and EBS placement were prospectively enrolled. Residual stones were evaluated by the check method. EBS was removed at the time of the check method or at a later time of residual stone removal. The primary outcome was to evaluate the efficacy of this check method. RESULTS: Residual CBD stone/sludge was detected in 20 of 56 patients (35.7%; stones: 28.6%, sludge: 7.1%) by the check method and removed by the ERCP procedure at a later time. After stent and final stone removal, patients were followed for an average of 211 days; cholangitis recurred in only 1.8% of patients. There were no adverse events associated with the check method. Temporary EBS prevented the recurrence of cholangitis by residual stone and caused no adverse events in the pancreatobiliary tract until the two-step check method (median, 113 days; range, 17-232 days). CONCLUSION: The new check method may be ideal and feasible for EBS removal because recurrences are very rare when a clear CBD has been verified, and an additional ERCP procedure is also possibly avoided.

Endoscopic Mucosal Resection of Adenocarcinoma at the Minor Duodenal Papilla: A Case Report and Suggestions for the Optimal Treatment Strategy.

We herein report an extremely rare case of adenocarcinoma of the minor duodenal papilla (MiDP) which was successfully treated by endoscopic mucosal resection (EMR). An asymptomatic 84-year-old man underwent upper gastrointestinal endoscopy, which revealed a slightly elevated lesion at the MiDP. The biopsy findings were suggestive of adenocarcinoma. Computed tomography, magnetic resonance images and endoscopic ultrasonography did not reveal pancreatic tumor infiltration nor any apparent distant metastases. Therefore, we treated the lesion using EMR with complete resection. No recurrence or metastasis has been detected at 13 months after EMR. Total resection of the MiDP can thus serve as a relatively safe and simple treatment.

Aerosols Produced by Upper Gastrointestinal Endoscopy: A Quantitative Evaluation.

INTRODUCTION: During the coronavirus disease 2019 pandemic, whether endoscopy generates aerosols needs to be determined. METHODS: In patients undergoing upper gastrointestinal endoscopy with an enclosure covering their heads, 0.3-10-µm aerosols were measured for 60 seconds before, during, and after endoscopy by an optical counter. Whether aerosols increased in the situation with and without endoscopy was examined. RESULTS: The analysis included 103 consecutive patients undergoing endoscopy and 90 control patients. Aerosols increased significantly during endoscopy compared with the control group. Body mass index and burping were significant factors related to increased aerosols during endoscopy. DISCUSSION: Upper gastrointestinal endoscopy was an aerosol-generating procedure.

Feasibility of endoscopic ultrasound-guided gallbladder drainage for acute cholecystitis patients receiving antithrombotic therapy.

BACKGROUND: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) as a treatment for patients with acute cholecystitis has been shown to obtain high technical and clinical success rates and a low recurrence rate. However, the safety of EUS-GBD for patients receiving antithrombotic therapy (ATT) has not been proven. The aim was to evaluate the safety and efficacy of EUS-GBD in patients receiving ATT. METHODS: Twelve patients with acute cholecystitis associated with gallstones who were receiving antithrombotic therapy and underwent EUS-GBD were enrolled in this retrospective study. Patients with grade II or III cholecystitis who had failed endoscopic transpapillary GBD (ETGBD) or developed recurrence after multiple ETGBD procedures underwent urgent drainage by EUS-GBD. The primary outcome was the rate of bleeding complications after the procedure and the secondary outcomes were the technical and clinical success rates, complications, and recurrence. RESULTS: Eleven (91.6%) patients underwent EUS-GBD with continuation of ATT (at least 1 agent). Five of 12 patients (41.7%) were receiving more than 1 agent for ATT. The rate of bleeding complications was 0% and the technical success rate was 100%, even though some patients had high-grade (severe) cholecystitis and/or several underlying diseases. Early complications were found in 2 (16.7%) patients. The clinical success rate was 91.7% (11/12). There were no recurrences of cholecystitis during the follow-up period (mean 261 [range 5-650] days). CONCLUSIONS: EUS-GBD yielded high technical and clinical success rates and a low recurrence rate. No patients receiving ATT developed bleeding complications. EUS-GBD might be a good option for patients on ATT.

Nickel-Catalyzed Asymmetric Friedel-Crafts Propargylation of 3-Substituted Indoles with Propargylic Carbonates Bearing an Internal Alkyne Group.

The nickel-catalyzed highly enantioselective Friedel-Crafts propargylation of 3-substituted indoles with propargylic carbonates bearing an internal alkyne group was developed. A wide array of the propargylic carbonates as well as 3-substituted indoles can be applicable to the asymmetric nickel catalysis, providing the corresponding chiral C-3 propargylated indolenine derivatives bearing two vicinal chiral centers in up to 89% yield with up to >99% ee and 94:6 dr (24 examples).

Ruthenium-catalyzed benzylic substitution of benzyl esters with stabilized carbon nucleophiles.

We have accomplished the ruthenium-catalyzed benzylic substitution of benzyl esters with a stabilized carbon nucleophile. A [Cp*RuCl2]2/picolinic acid catalyst system promoted the reaction of 2-naphthylmethyl-2,3,4,5,6-pentafluorobenzoates with a series of stabilized carbon nucleophiles such as malonates, ß-ketoesters, and diketones to give the corresponding benzylic alkylation products in moderate to high yields. We proposed a plausible reaction mechanism that could involve a (π-benzyl)ruthenium intermediate.

Nickel-Catalyzed Hydroarylation of in Situ Generated 1,3-Dienes with Arylboronic Acids Using a Secondary Homoallyl Carbonate as a Surrogate for the 1,3-Diene and Hydride Source.

The nickel-catalyzed hydroarylation of 1,3-dienes with arylboronic acids using a secondary homoallyl carbonate as a surrogate for the 1,3-diene and hydride source has been developed. The synthetic strategy allowed an efficient access to a wide array of hydroarylation products in high yields with high functional group compatibility without the use of an external hydride source. Mechanistic experiments indicated that the alkene-directed oxidative addition and subsequent ß-hydride elimination would be a critical process in this transformation.

Synthesis of substituted benzo[b][1,4]oxazepine derivatives by the reaction of 2-aminophenols with alkynones.

We have developed a novel synthetic method accessing benzo[b][1,4]oxazepines that are one of the rare classes of benzoxazepine derivatives by reaction of 2-aminophenols with alkynones in 1,4-dioxane at 100 °C. A series of benzo[b][1,4]oxazepine derivatives can be prepared by using this synthetic protocol. Mechanistic experiments indicated that the hydroxy proton of the aminophenol could play a crucial role in the formation of an alkynylketimine intermediate that undergoes 7-endo-dig cyclization.

Nickel-Catalyzed Transformation of Alkene-Tethered Oxime Ethers to Nitriles by a Traceless Directing Group Strategy.

Nickel-catalyzed transformation of alkene-tethered oxime ethers to nitriles using a traceless directing group strategy has been developed. A series of alkene-tethered oxime ethers derived from benzaldehyde and cinnamyl aldehyde derivatives were converted into the corresponding benzonitriles and cinnamonitriles in 46-98% yields using the nickel catalyst system. Control experiments showed that the alkene group tethered to an oxygen atom on the oximes via one methylene unit plays a key role as a traceless directing group during the catalysis.

Nickel-Catalyzed Benzylic Substitution of Benzyl Esters with Malonates as a Soft Carbon Nucleophile.

The nickel-catalyzed benzylic substitution of benzyl alcohol derivatives with a soft carbon nucleophile is extremely rare compared to that with a hard carbon nucleophile. We have achieved the nickel-catalyzed benzylic substitution of benzyl esters with malonates as a soft carbon nucleophile. Primary and secondary benzyl 2,3,4,5,6-pentafluorobenzoates as well as a wide variety of malonate derivatives were well tolerated in the nickel-catalyzed reaction, providing the corresponding alkylation products in 46-86% yields (34 examples). Additionally, we propose a possible reaction mechanism that would undergo via the η1- and η3-benzylnickel intermediates.

Synthesis of benzoxazoles via the copper-catalyzed hydroamination of alkynones with 2-aminophenols.

We describe herein the synthetic method to benzoxazole derivatives via the copper-catalyzed hydroamination of alkynones with 2-aminophenols. The method produced a wide variety of functionalized benzoxazole derivatives in good yields. Preliminary mechanistic experiments revealed that the reaction would proceed through the copper-catalyzed hydroamination of alkynones and the sequential intramolecular cyclization of ß-iminoketones/elimination of acetophenone promoted by the copper catalyst.

Mechanistic insight into the catalytic hydrogenation of nonactivated aldehydes with a Hantzsch ester in the presence of a series of organoboranes: NMR and DFT studies.

Mechanistic studies on the organoborane-catalyzed transfer hydrogenation of nonactivated aldehydes with a Hantzsch ester (diethyl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) as a synthetic NADH analogue were performed by NMR experiments and DFT calculations. In the reaction of benzaldehyde with the Hantzsch ester, the catalytic activity of tris[3,5-bis(trifluoromethyl)phenyl]borane was superior to that of other borane catalysts, such as tris(pentafluorophenyl)borane, trifluoroborane etherate, or triphenylborane. Stoichiometric NMR experiments demonstrated that the hydrogenation process proceeds through activation of the aldehyde by the borane catalyst, followed by hydride transfer from the Hantzsch ester to the resulting activated aldehyde. DFT calculations for the hydrogenation of benzaldehyde with the Hantzsch ester in the presence of borane catalysts supported the reaction pathway and showed why the catalytic activity of tris[3,5-bis(trifluoromethyl)phenyl]borane is higher than that of the other boron catalysts. Association constants and Gibbs free energies in the reaction of boron catalysts with benzaldehyde or benzyl alcohol, which were investigated by 1H NMR analyses, also indicated why tris[3,5-bis(trifluoromethyl)phenyl]borane is a superior catalyst to tris(pentafluorophenyl)borane, trifluoroborane etherate, or triphenylborane in the hydrogenation reaction.

Nickel-Catalyzed Asymmetric Propargylic Amination of Propargylic Carbonates Bearing an Internal Alkyne Group.

We have achieved the nickel-catalyzed asymmetric propargylic amination of propargylic carbonates bearing an internal alkyne group. A wide variety of propargylic carbonates and N-methylaniline derivatives were tolerated under the reaction conditions, providing the corresponding chiral propargylic amines in up to 97% yield with up to 97% ee.

Endoscopic ultrasound-guided transduodenal drainage of idiopathic retroperitoneal abscess in an immunocompromised patient: A case report.

RATIONALE: Idiopathic retroperitoneal abscesses are insidious, occult illnesses with high mortality if inadequately drained. Endoscopic ultrasound-guided drainage is an alternative to percutaneous or surgical drainage, it is not widely performed for retroperitoneal abscesses other than peripancreatic fluid collection. PATIENT CONCERNS: We present a 76-year-old Japanese woman with abdominal pain, high fever, and a history of rheumatism on treatment with immunosuppressants. DIAGNOSES: The patient was diagnosed with idiopathic retroperitoneal abscess based on results obtained from her clinical course and findings on computed tomography. INTERVENTIONS: We performed Endoscopic ultrasound-guided drainage. After we performed needle puncture via the descending portion of the duodenum, the fistula was expanded using a dilator, and a double-pigtail stent and endoscopic nasobiliary drainage tube were inserted. OUTCOMES: The patient was kept nil by mouth, together with intravenous antibiotic therapy, and repeated washing of the abscess cavity with saline was performed. After that, we confirmed disappearance of the cavity, and, after removing the tubes, commenced oral feeding. We were able to avoid surgery in this immunosuppressed patient. LESSONS: Endoscopic ultrasound (EUS)-guided abscess drainage can be overall considered a safe and useful procedure. We also propose the double-stent method, with both internal and external stents, for the treatment of idiopathic retroperitoneal abscesses.

Hydroxy-Directed Amidation of Carboxylic Acid Esters Using a Tantalum Alkoxide Catalyst.

We describe herein a new strategy for the chemoselective synthesis of amides by using a metal-catalyzed hydroxy-directed reaction. A hydroxy group located at the ß-position of an ester group promoted the activation of a carbonyl group with a tantalum alkoxide catalyst followed by amidation reactions, leading to a wide variety of ß-hydroxyamides with excellent chemeselectivity. The chemoselective amidation strategy can be extended to the catalytic synthesis of dipeptide derivatives, which remains challenging research subjects in modern organic synthesis.

The C-terminal fragment of prostate-specific antigen, a 2331 Da peptide, as a new urinary pathognomonic biomarker candidate for diagnosing prostate cancer.

BACKGROUND AND OBJECTIVES: Prostate cancer (PCa) is one of the most common cancers and leading cause of cancer-related deaths in men. Mass screening has been carried out since the 1990s using prostate-specific antigen (PSA) levels in the serum as a PCa biomarker. However, although PSA is an excellent organ-specific marker, it is not a cancer-specific marker. Therefore, the aim of this study was to discover new biomarkers for the diagnosis of PCa. MATERIALS AND METHODS: We focused on urine samples voided following prostate massage (digital rectal examination [DRE]) and conducted a peptidomic analysis of these samples using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS(n)). Urinary biomaterials were concentrated and desalted using CM-Sepharose prior to the following analyses being performed by MALDI-TOF/MS(n): 1) differential analyses of mass spectra; 2) determination of amino acid sequences; and 3) quantitative analyses using a stable isotope-labeled internal standard. RESULTS: Multivariate analysis of the MALDI-TOF/MS mass spectra of urinary extracts revealed a 2331 Da peptide in urine samples following DRE. This peptide was identified as a C-terminal PSA fragment composed of 19 amino acid residues. Moreover, quantitative analysis of the relationship between isotope-labeled synthetic and intact peptides using MALDI-TOF/MS revealed that this peptide may be a new pathognomonic biomarker candidate that can differentiate PCa patients from non-cancer subjects. CONCLUSION: The results of the present study indicate that the 2331 Da peptide fragment of PSA may become a new pathognomonic biomarker for the diagnosis of PCa. A further large-scale investigation is currently underway to assess the possibility of using this peptide in the early detection of PCa.

Ruthenium-catalyzed regio- and enantioselective allylic amination of racemic 1-arylallyl esters.

The regio- and enantioselective allylic amination of racemic monosubstituted allylic esters, such as 1-arylallyl acetates, with cyclic secondary amines has been accomplished. The RuCl3/(S,S)-ip-pybox catalyst system has effectively catalyzed the reaction to afford the enantiomerically enriched branch-type allylic amines with perfect regioselectivity and high enantioselectivity.

Significance of semiquantitative assessment of preformed donor-specific antibody using luminex single bead assay in living related liver transplantation.

AIM: To analyze the risks of preoperatively produced donor-specific antibody (DSA) in liver transplantation. METHODS: DSA was assessed using direct complement-dependent cytotoxicity (CDC) and anti-human globulin- (AHG-) CDC tests, as well as the Luminex Single Antigen assay. Among 616 patients undergoing blood type identical or compatible living donor liver transplantation (LDLT), 21 patients were positive for CDC or AHG-CDC tests, and the preserved serum from 18 patients was examined to determine targeted Class I and II antigens. The relationships between the mean fluorescence intensity (MFI) of DSA and the clinical outcomes were analyzed. RESULTS: Patients were divided into 3 groups according to the MFI of anti-Class I DSA: high (11 patients with MFI > 10,000), low (2 patients with MFI < 10,000), and negative (5 patients) MFI groups. Six of 11 patients with high Class-I DSA showed positive Class-II DSA. Hospital death occurred in 7 patients of the high MFI group. High MFI was a significant risk factor for mortality (P = 0.0155). Univariate analysis showed a significant correlation between MFI strength and C4d deposition (P = 0.0498). CONCLUSIONS: HLA Class I DSA with MFI > 10,000 had a significant negative effect on the clinical outcome of patients with preformed DSA in LDLT.